A study of the reciprocal connections between the septum and the entorhinal area using anterograde and retrograde axonal transport methods in the rat brain.
The reciprocal connections between the septum and the entorhinal area (EA) was studied in the rat brain using antero- and retrograde axonal transport methods. After injections of large volumes (2 X 100 nl) of horseradish peroxidase (HRP) conjugated to wheat-germ agglutinin (WGA) into the medial septum (MS) and the diagonal band of Broca (dbB), anterogradely transported HRP-WGA was found primarily in layers II and IV of the medial and lateral EA. Injections of HRP-WGA (50-100 nl) or fluorescent dyes (50-100 nl) into different parts of the retrohippocampal region resulted in labeling, by retrograde axonal transport, of cells in the MS and dbB, both ipsi- and contralateral to the injected hemisphere. The labeled cells were either small (long axis of soma: 10-15 micron), round, and oval, or medium (15-25 micron) to large (25-35 micron) of fusiform or multipolar shape. By using the method of retrograde fluorescent double labeling, the septal afferents to the EA were found to give off collaterals to other parts of the hippocampal region. A much smaller number of septal cells appeared to send bilateral projections to the EA of both hemispheres. Studies employing retrograde transport of HRP in combination with acetylcholinesterase (AChE) histochemistry on the same tissue section showed that, while a large number of cells projecting to the EA contain AChE, many projecting cells are devoid of AChE reaction products. These findings suggest that the septo-entorhinal projection consists of a cholinergic as well as a noncholinergic component. The entorhinal efferents to the septum were studied after injections of HRP-WGA into different parts of the retrohippocampal region. Labeled fibers could be traced through the fimbria to their terminal fields in the intermediate parts of the lateral septal nucleus and to the most lateral aspect of the vertical limb of the dbB. The cells giving rise to this projection were situated in layer IV of the medial and layers II through V of the lateral EA. Taken together, the present findings demonstrate a close anatomical relationship between the septum and the entorhinal area, in addition to the better known connections between the septum and the Ammon's horn.


Effect of cooling and heating on the regional distribution of blood flow in fetal sheep.
This is a study on the effect of cooling and heating amniotic fluid on blood flow to fetal tissues and organs. In 8 unanaesthetized, chronically-catheterised fetal sheep (129-137 days gestation) cold or warm water was passed through tubing encircling the fetus in utero and blood flow was measured using the radionuclide-labelled 15 mu spheres. Following cooling for 30 min, amniotic fluid temperature fell 9.6 degrees C to 29.9 +/- 2.1 degrees C (SEM) fetal arterial temperature fell 2.37 degrees C to 37.30 +/- 0.36, and maternal arterial temperature fell 0.53 degrees C to 38.58 +/- 0.16. Blood flow through the fetal skin fell 60% (P less than 0.01) to 13.6 ml/min per 100 g tissue. Blood flow to the brown fat increased 186% (P less than 0.05) to 99.6 ml/min per 100 g. Following warming for 20 min, fetal temperature rose to 40.43 +/- 0.19 degrees C, and skin blood flow did not change significantly relative to initial control period but rose 200% above that during cooling (P less than 0.01). During both cooling and heating, blood flow to the adrenals rose significantly (P less than 0.05) whereas flow to the carcass, brain, kidneys, and placenta was not altered detectably. Continuous sampling of blood from the inferior vena cava during microsphere injection failed to detect any evidence of arterio-venous shunting through the skin at any temperature studied. Overall, the blood flow responses are consistent with a thermoregulatory role for the skin and brown fat in the near-term fetal sheep.


RTD modeling of a continuous dry granulation process for process control and materials diversion.
Disturbance propagation during continuous manufacturing processes can be predicted by evaluating the residence time distribution (RTD) of the specific unit operations. In this work, a dry granulation process was modelled and four scenarios of feeding events were simulated. We performed characterization of the feeders and developed RTD models for the blender and the roller compactor based on impulse-response measurements via color tracers. Out-of-specification material was defined based on the active pharmaceutical ingredient (API) concentration. We calculated the amount of waste material at various diversion points, considering four feeder-related process-upset scenarios and formulated considerations for the development of a control concept. The developed RTD models allow material tracking of materials that may be used for following the spread contaminants within the process and for batch definition. The results show that RTD modeling is a valuable tool for process development and design, as well as for process monitoring and material tracking.


Maternal natal environment and breeding territory predict the condition and sex ratio of offspring.
Females in a variety of taxa adjust offspring sex ratios to prevailing ecological conditions. However, little is known about whether conditions experienced during a female's early ontogeny influence the sex ratio of her offspring. We tested for past and present ecological predictors of offspring sex ratios among known-age females that were produced as offspring and bred as adults in a population of house wrens. The body condition of offspring that a female produced and the proportion of her offspring that were male were negatively correlated with the size of the brood in which she herself was reared. The proportion of sons within broods was negatively correlated with maternal hatching date, and varied positively with the quality of a female's current breeding territory as predicted. However, females producing relatively more sons than daughters were less likely to return to breed in the population the following year. Although correlative, our results suggest that the rearing environment can have enduring effects on later maternal investment and sex allocation. Moreover, the overproduction of sons relative to daughters may increase costs to a female's residual reproductive value, constraining the extent to which sons might be produced in high-quality breeding conditions. Sex allocation in birds remains a contentious subject, largely because effects on offspring sex ratios are small. Our results suggest that offspring sex ratios are shaped by various processes and trade-offs that act throughout the female life history and ultimately reduce the extent of sex-ratio adjustment relative to classic theoretical predictions.


Porous Mn2 O3 : A Low-Cost Electrocatalyst for Oxygen Reduction Reaction in Alkaline Media with Comparable Activity to Pt/C.
Preparing nonprecious metal catalysts with high activity in the oxygen reduction reaction (ORR) can promote the development of energy conversion devices. Support-free porous Mn2 O3 was synthesized by a facile aerosol-spray-assisted approach (ASAA) and subsequent thermal treatment, and exhibited ORR activity that is comparable to commercial Pt/C The catalyst also exhibits notably higher activity than other Mn-based oxides, such as Mn3 O4 and MnO2 . The rotating ring disk electrode (RRDE) study indicates a typical 4-electron ORR pathway on Mn2 O3 . Furthermore, the porous Mn2 O3 demonstrates considerable stability and a good methanol tolerance in alkaline media. In light of the low cost and high earth abundance of Mn, the highly active Mn2 O3 is a promising candidate to be used as a cathode material in metal-air batteries and alkaline fuel cells.


SARS-CoV-2 Wastewater Surveillance for Public Health Action.
Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has garnered extensive public attention during the coronavirus disease pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantification of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, bridging the communication and knowledge gaps between researchers and public health responders is needed. We describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethics consideration for monitoring. Although wastewater surveillance to assess community infections is not a new idea, the coronavirus disease pandemic might be the initiating event to make this emerging public health tool a sustainable nationwide surveillance system, provided that these barriers are addressed.


A reference preparation of buffalo pituitary follicle stimulating hormone using lectin affinity chromatography.
An improved and cost effective method to isolate FSH from buffalo pituitary glands is described here. The buFSH activity was monitored throughout by a highly sensitive heterologous radioimmunoassay (sensitivity 0.2 ng oFSH/mL) and the in vivo biological activity of the final preparation was also established. A biologically active buFSH-enriched preparation with a moderate recovery (42%) was obtained. The yield of the final buFSH-enriched preparation was 26.5 mg/kg of buffalo pituitary gland. In SDS-PAGE, the purified buFSH resolved as a heterodimer of 30 kDa molecular size, with a 21 kDa presumptive alpha-subunit. This preparation was also characterized in terms of biological and some of its physicochemical properties. A high-titer antiserum to buFSH was also raised in rabbit using this preparation. The reagents generated, buFSH and buFSH-specific polyclonal antisera, have possible diagnostic and therapeutic usage for improvement of reproductive health of water buffaloes.


Toxicities of 166Holmium-chitosan in mice.
166Holmium (166Ho) is a radionuclide of rare earth chemical and is known to have antitumor activity. Several chemicals were complexed with 166Ho to facilitate the transport of this radionuclide to the site of action. In this study, 166Ho was complexed to chitosan (Chit) which decreases the distribution of Ho into other tissues when applied intrahepatically. To investigate the single dose toxicity, mice were administered intravenously with 1 mCi/kg body weight of 166Ho-Chit (DW-166HC), Chit or nothing. Organ weights, hematological and histopathological studies were performed in 6 animals per group at 1, 3 and 14 days after administration. In 166Ho-Chit treated animals, a slight decrease of erythrocyte number was observed at day 14 and increases of relative liver and lung weights were found at day 3. Although marked multiple necrotic foci in the white pulp and depletion of marginal zone in the spleen were noted at day 1, these findings were decreased in severity and fully recovered at day 3 and day 14, respectively. Slightly decreased kidney weights were observed both in Chit and in 166Ho-Chit treated groups without histological alterations. Thus it is suggested that most effects of 166Ho-Chit observed at an early stage after administration are limited to rapidly dividing cells and reversible within 14 days.


Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody.
Anti-neutrophil cytoplasmic antibody directed against myeloperoxidase (MPO-ANCA) has been implicated in pauci-immune crescentic glomerulonephritis. It stimulates primed neutrophils to adhere to glomerular endothelial cells (GECs), thereby releasing reactive oxygen and other toxic substances and ultimately damaging the GECs. Though, a pathogenic role for MPO-ANCA is not fully understood, we hypothesized that MPO-ANCA modulates GEC functions by the increases in expression of adhesion molecules. A polyclonal rabbit anti-recombinant mouse MPO antibody (anti-rmMPO IgG) was evaluated in mouse GEC (mGEC) for its effect on adhesion molecule expression. The primary culture of mGEC was incubated with anti-rmMPO IgG or isotype control and the expression of intercellular adhesion molecules-1 (ICAM-1) was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis and ICAM-1 cell ELISA. The real-time RT-PCR analysis showed that a treatment with 100 microg/ml anti-rmMPO IgG increased the expression of mRNAs for ICAM-1, vascular cell adhesion molecule-1 and E-selectin by approximately 12.5, 7.5 and 10.5-fold, respectively. ICAM-1 cell ELISA also substantiated increased expression of ICAM-1. This enhancement of ICAM-1 expression was mediated by the antigen specificity of anti-rmMPO IgG. In addition, there were several proteins in mGEC specifically immunoprecipitated with anti-rmMPO IgG. These results showed that anti-MPO antibody activates not only neutrophils, but also GEC, indicating that anti-rmMPO IgG-induced direct activation of GEC contributes to neutrophil adhesion to GEC, thereby increasing glomerular neutrophil infiltration in initiation and progression of pauci-immune glomerulonephritis.


[Accuracy of Berlin questionnaire with different body mass index cutoff values in the screening of patients with obstructive sleep apnea].
Objective: To evaluate the accuracy of Berlin questionnaire in the screening of patients with obstructive sleep apnea (OSA), after using different body mass index (BMI) cutoff values. Methods: The data were collected from September, 2011 to May, 2012 at the Sleep Medicine Center of West China Hospital, Sichuan University (Chengdu, China). A total of 350 consecutive patients (302 males and 48 females, 19-68 years old, average (42.9±11.0) years old) with suspected OSA who underwent an overnight polysomnography (PSG) were recruited into this study. Berlin questionnaire was completed. Based on the severity of OSA which were determined by apnea-hypopnea index (AHI), the patients were classified into four groups of primary snoring (<5 events/h), mild (5-<15 events/h), moderate (15-<30 events/h) and severe OSA (≥30 events/h). Sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics curve of Berlin questionnaire with different BMI cutoff values were calculated. Results: In patients with BMI≥30 kg/m(2,) to diagnose mild-moderate-severe (AHI≥5 events/h), moderate-severe (AHI≥15 events/h), and severe (AHI≥30 events/h) OSA, the sensitivity of Berlin questionnaire were 69.2%, 71.6%, and 76.6%; the negative predictive values were 15.7%, 33.0%, and 56.5%, respectively. In patients with BMI≥24 kg/m(2,) questionnaire had the highest sensitivity (94.3%, 94.8%, and 96.7%, respectively) and negative predictive values (28.0%, 44.0%, and 72.0%, respectively). Conclusions: When BMI cutoff values gradually declines, the sensitivity and negative predictive values of Berlin questionnaire increase, but the specificity and positive predictive values decline. The accuracy of Berlin questionnaire possibly is related to BMI cutoff values.


Molecular electronics: insight from first-principles transport simulations.
Conduction properties of nanoscale contacts can be studied using first-principles simulations. Such calculations give insight into details behind the conductance that is not readily available in experiments. For example, we may learn how the bonding conditions of a molecule to the electrodes affect the electronic transport. Here we describe key computational ingredients and discuss these in relation to simulations for scanning tunneling microscopy (STM) experiments with C60 molecules where the experimental geometry is well characterized. We then show how molecular dynamics simulations may be combined with transport calculations to study more irregular situations, such as the evolution of a nanoscale contact with the mechanically controllable break-junction technique. Finally we discuss calculations of inelastic electron tunnelling spectroscopy as a characterization technique that reveals information about the atomic arrangement and transport channels.


Studies of the precipitation pattern of paclitaxel in intravenous infusions and rat plasma using laser nephelometry.
Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma.


Ketamine augmentation rapidly improves depression scores in inpatients with treatment-resistant bipolar depression.
To study the clinical effect of a single ketamine infusion, 0.5 mg/kg body weight, in bipolar depressive patients receiving mood-stabilising drugs, not improving on antidepressants. Previously, in such patients, we had found a correlation between clinical efficacy, serum brain-derived neurotrophic factor and vitamin B12 levels and a rapid improvement in neurocognitive performance. The study included 53 patients (13 men, 40 women), aged 22-81 years, receiving ≥1 mood-stabilising medications of the first and/or second generation. Pre-infusion depression intensity on the Hamilton Depression Rating Scale (HDRS) was 23.4 ± 4.6 points and the assumed criterion for response was a reduction of ≥50% in the HDRS score after 7 days. Twenty-seven subjects (51%) met a criterion for response, more frequently males (77%) than females (43%). Responders did not differ from non-responders as to age, illness onset, duration of depressive episode, type of bipolar illness, family history of psychiatric illness, personal/family history of alcoholism or using lithium, quetiapine or a combination of these mood stabilisers. The results confirm a rapid antidepressant effect of ketamine infusion in a considerable proportion of those patients with bipolar depression receiving mood-stabilising drugs. Apart from male gender, no other clinical factors were predictors of response.


Associations between Interleukin-31 Gene Polymorphisms and Dilated Cardiomyopathy in a Chinese Population.
To explore the role of Interkeulin-31 (IL-31) in dilated cardiomyopathy (DCM), in our study, two SNPs of IL-31, rs4758680 (C/A) and rs7977932 (C/G), were analyzed in 331 DCM patients and 493 controls in a Chinese Han population. The frequencies of C allele and CC genotype of rs4758680 were significantly increased in DCM patients (P = 0.005, P = 0.001, resp.). Compared to CC genotype of rs4758680, the A carriers (CA/AA genotypes) were the protect factors in DCM susceptibility while the frequencies of CA/AA genotypes were decreased in the dominant model for DCM group (P < 0.001, OR = 0.56, 95%CI = 0.39-0.79). Moreover, IL-31 mRNA expression level of white blood cells was increased in DCM patients (0.072 (0.044-0.144) versus 0.036 (0.020-0.052), P < 0.001). In survival analysis of 159 DCM patients, Kaplan-Meier curve revealed the correlation between CC homozygote of rs4758680 and worse prognosis for DCM group (P = 0.005). Compared to CC genotype, the CA/AA genotypes were the independent factors in both univariate (HR = 0.530, 95%CI = 0.337-0.834, P = 0.006) and multivariate analyses after age, gender, left ventricular end-diastolic diameter, and left ventricular ejection fraction adjusted (HR = 0.548, 95%CI = 0.345-0.869, P = 0.011). Thus, we concluded that IL-31 gene polymorphisms were tightly associated with DCM susceptibility and contributed to worse prognosis in DCM patients.


Carbamazepine and phenytoin inhibit somatostatin release from dispersed cerebral cells in culture.
To elucidate the mechanism by which carbamazepine lowers somatostatin concentration in cerebrospinal fluid of humans, the effect of carbamazepine on secretion of this peptide was studied in rat cerebral cell cultures. Concentrations of carbamazepine within the therapeutic range (4 x 10(-5) M) inhibited spontaneous release of somatostatin and blocked secretory responses to the epileptogen, picrotoxin, and to the cyclic cAMP stimulator forskolin. One of the proposed mechanisms of carbamazepine action is that it binds to adenosine receptors, but in this study, aminophylline, an adenosine antagonist, in a concentration as high as 2.4 x 10(-4) M, did not reverse carbamazepine effects. Carbamazepine suppression of picrotoxin, however, was overcome by exposure to veratridine, a sodium channel-active compound. This finding supports the hypothesis that carbamazepine acts by binding to sodium channels. Phenytoin, another anticonvulsant with many similar properties, also blocked picrotoxin-induced somatostatin release at a concentration of 10(-4) M, and its effects were also reversed by veratridine at a concentration of 10(-5) M. These findings clarify the mechanism by which carbamazepine and phenytoin act in epilepsy and trigeminal neuralgia.


Finerenone.
In developed countries, diabetes mellitus (DM) is one of the main causes of end stage renal disease (ESRD). In addition, the development of chronic kidney disease (CKD) further increases the already significantly increased cardiovascular (CV) risk in patients with diabetes. Both albuminuria and impaired renal function predict CV disease-related morbidity. The multifactorial pathogenesis of DM-related CKD involves structural, physiological, hemodynamic, and inflammatory processes. Instead of a so-called glucocentric approach, current evidence suggests that a multimodal, interdisciplinary treatment approach is needed to also prevent further progression of CKD and reduce the risk of cardiovascular events. Combined antihypertensive, antihyperglycemic and hypolipidemic therapy is the basis of a comprehensive approach to prevent the progression of diabetic kidney disease. According to recent evidence, adjunctive therapy with the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone - in addition to the use of an ACE (angiotensin converting enzyme) or AT1 (angiotensin II receptor subtype 1) blocker and an SGLT2 (sodium-glucose cotransporter-2) inhibitor - represents an effective therapeutic tool to improve nephroprotection in CKD. The aim of this review is to provide brief information on this promising pharmacotherapeutic approach to the treatment of diabetic kidney disease.


Combination Strategies on the Basis of Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer: Where Do We Stand?
The era of immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies in the treatment of advanced non-small-cell lung cancer (NSCLC) is coming. Because of the lack of the definite biomarkers to select the optimal responders, only approximately 20% of patients with advanced NSCLC would respond to single checkpoint inhibitors-based immunotherapy. Moreover, primary or acquired resistance to conventional therapies is inevitable in most cases. Thus, combinations are pushed to move forward to be an alternative strategy and surely, it would be a future direction. Combination approaches on the basis of PD-1/PD-L1 inhibitors are currently designed to re-energize the immune system with complementary/synergetic mechanisms and could achieve durable antineoplastic effects in NSCLC. Herein, we highlight the potential combinations on the basis of PD-1/PD-L1 inhibitors in NSCLC, with other immunotherapies, chemotherapy, radiotherapy, and targeted therapy in this current review.


Prostaglandin F2 alpha (PGF2 alpha) triggers protein kinase C (PKC) and tyrosine kinase activity in cultured mammalian cells.
Prostaglandin F2 alpha (PGF2 alpha) added to confluent resting Swiss 3T3 cells triggers tyrosine kinase (PTK) activation characterized by the phosphorylation of a set of 75, 86, 110 and 140 kD proteins. PGF2 alpha induces this event independently of PKC activation. However, both PKC and PTK activities appear to act concertedly to cause mitogenesis. Here we discuss their relevance in the control of mammalian cell division.


Coinheritance of a Rare Nucleotide Substitution on the β-Globin Gene and Other Known Mutations in the Globin Clusters: Management in Genetic Counseling.
A large number of methods for DNA analysis are available to identify defects in globin genes associated with hemoglobin (Hb) disorders. In this study, we report a rare nucleotide (nt) substitution on the β-globin gene, nt 781 in the second intron [IVS-II-781 (C > G); HBB: c.316-70C > G], identified in four patients. This nt substitution was previously described only as a personal communication to the HbVar database and indicated as a β(0) or β(+) mutation. The purpose of this study was to evaluate the clinical implication of this nt change, particularly when coinherited with severe β-thalassemia (β-thal), in order to be able to conduct appropriate genetic counseling. Genetic studies were performed on two subjects, one carried Hb S [β6(A3)Glu→Val; HBB: c.20A > T], and the other carried IVS-I-110 (G > A) (HBB: c.93-21G > A). All these subjects showed this new β nt substitution in association with Hb A2' (or Hb B2) [δ16(A13)Gly→Arg; HBD: c.49G > C]. Another 16 samples, carrying the same δ variant as the probands, were processed by β-globin gene sequencing in order to better understand the correlation between this Hb variant and the rare nt substitution reported in this study. The present investigation emphasizes the importance of sharing the observed nt changes in the globin gene cluster, especially in the case of new or rare undefined mutations, in order to facilitate the determination of their phenotypic expression, the possible interactions with known molecular defects and to formulate appropriate genetic counseling for at-risk couples.


The search for a promising cell factory system for production of edible vaccine.
Despite worldwide vaccination against devastating diseases for decades, millions of children in remote and impoverished regions of the globe die every year from vaccine-preventable infectious diseases. The reasons for incomplete coverage of vaccination programs are based in part on the relatively high costs of conventional vaccinations, including mass production, refrigeration, transportation, and training as well as funding personnel for their administration. Plant-based edible vaccines (PEVs) have been introduced as a revolutionary cost-effective vaccination modality. However, they suffer from major deficiencies that have restricted their application to bench-scale. This article discusses the deficiencies of PEVs and also provides concise overview on the health-promoting, biological and biotechnological features of spirulina (Arthrospira). In short, we envision that spirulina could be considered as a potential alternative biofactory system to the plants toward the production of edible vaccines in high-yield with low-costs that other hosts cannot yet offer.


Type C Pancreaticobiliary Maljunction Is Associated With Perforated Choledochal Cyst in Children.
Background: Perforation of a choledochal cyst (CC) is not rare, but the pathogenesis of spontaneous perforation has not been established. Pancreaticobiliary maljunction (PBM) is commonly seen in association with choledochal cyst. To explore the relationship between PBM and perforated CC, a retrospective study was conducted. Methods: We analyzed all the patients with CC who underwent surgery in our hospital from 2014.06.01 to 2018.12.31. All patients were divided into two groups: group 1 were patients with perforated CC, and group 2 were patients with non-perforated CC. We recalled all the patients records to identify types of PBM. PBM was divided into four types [(A) stenotic type, (B) non-stenotic type, (C) dilated channel type, and (D) complex type] according to the classification proposed by the Committee on Diagnostic Criteria of the Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) in 2015. Results: There were 186 patients with CC in all, and 116 patients showed PBM. Twenty patients in group 1 and 96 patients in group 2. There was an extremely higher percentage of type C PBM in group 1 than in group 2 (60 and 17.7%, respectively). More fusiform dilatation cases were found in group 1 (70%) than in group 2 (58.3%). Also there were more type C PBM in fusiform cases and type A PBM were frequently seen in cystic cases (P < 0.01). Conclusions: We found that Type C PBM and fusiform common bile duct maybe relate to the perforation of choledochal cyst. Patients with type C PBM and fusiform common bile duct should be treated more proactively, preferably before they perforate.


European Society of Gynaecological Oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery.
The European Society of Gynaecological Oncology (ESGO) developed and established for the first time in 2016, and updated in 2020, quality indicators for advanced ovarian cancer surgery to audit and improve clinical practice in Europe and beyond. As a sequela of the continuous effort to improve oncologic care in patients with ovarian cancer, ESGO issued in 2018 a consensus guidance jointly with the European Society of Medical Oncology addressing in a multidisciplinary fashion 20 selected key questions in the management of ovarian cancer, ranging from molecular pathology to palliation in primary and relapse disease. In order to complement the above achievements and consolidate the promoted systemic advances and surgical expertise with adequate peri-operative management, ESGO developed, as the next step, clinically relevant and evidence-based guidelines focusing on key aspects of peri-operative care and management of complications as part of its mission to improve the quality of care for women with advanced ovarian cancer and reduce iatrogenic morbidity. To do so, ESGO nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of ovarian cancer (18 experts across Europe). To ensure that the guidelines are evidence based, the literature published since 2015, identified from a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 117 independent international practitioners in cancer care delivery and patient representatives.


Mycosis fungoides: a dermatological masquerader.
Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of MF can be difficult due to highly variable presentations and the sometimes nonspecific nature of histological findings. Molecular biology has improved the diagnostic accuracy. Nevertheless, clinical experience is of substantial importance as MF can resemble a wide variety of skin diseases. We performed a literature review and found that MF can mimic >50 different clinical entities. We present a structured framework of clinical variations of classical, unusual and distinct forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic (including syringotropic and folliculotropic) MF, MF with follicular mucinosis, granulomatous MF with granulomatous slack skin and papuloerythroderma of Ofuji are delineated in more detail.


Motoneuron firing in amyotrophic lateral sclerosis (ALS).
Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials.


Tocopherol mobilization during dynamic exercise after beta-adrenergic blockade.
This study addresses the question of whether tocopherol mobilization during exercise could be explained by a lipolysis effect. Nine healthy male subjects were submitted to dynamic exercise of graded intensity (45, 60, 75% VO2max) on a cycle ergometer after ingestion of either a placebo or 40 mg propranolol as beta-blocker. Plasma tocopherol concentration increased toward a peak value reached during or at the end of exercise. The magnitude of this increase did not differ in the two experimental conditions while plasma free fatty acids concentration was lowered under beta-adrenergic blockade by propranolol. From these results, we conclude that tocopherol mobilization during dynamic exercise does not depend on lipolysis.


Neurological disorders associated with glutamic acid decarboxylase 65 antibodies: Clinical spectrum and prognosis of a cohort from China.
To describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China. In this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients. Fifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6-33.75 month, range 3-96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients. LE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.


Cis-acting elements stimulating kinetoplastid guide RNA-directed editing.
The coding sequence of several mitochondrial mRNAs of the kinetoplastid protozoa is created through the insertion and deletion of specific uridylates. The editing reactions are required to be highly specific in order to ensure that functional open reading frames are created in edited mRNAs and that potentially deleterious modification of normally nonedited sequence does not occur. Selection-amplification and mutagenesis were previously used to identify the optimal sequence requirements for in vitro editing. There is, however, a minority of natural editing sites with suboptimal sequence. Several cis-acting elements, obtained from an in vitro selection, are described here that are able to compensate for a suboptimal editing site. An A + U sequence element within the 5'-untranslated region of cytochrome b mRNA from Leishmania tarentolae is also demonstrated to function as a cis-acting guide RNA and is postulated to compensate for a suboptimal editing site in vivo. Two proteins within an enriched editing extract are UV-cross-linked to two different in vitro selected editing substrates more efficiently than poorly edited RNAs. The results suggest that these proteins contribute to the specificity of the editing reaction.


A computer model of intracranial dynamics integrated to a full-scale patient simulator.
The ability to visualize intracranial dynamics during simulated clinical scenarios is a valuable tool for teaching brain physiology and the consequences of different medical interventions on the brain. Studies have isolated physiologic variables and shown their effects on brain dynamics. However, no studies have shown the combined effects of these variables on intracranial dynamics. This brain model offers one approach that brings all these relationships together and shows how they affect the dynamics of the brain. The brain model obtains its physiologic inputs from a full-scale patient simulator which responds to clinical interventions. This integration allows individuals working on the patient simulator to see the effects of their actions on brain dynamics. The brain model gives a real-time display of intracranial events (cerebral metabolic rate, cerebral blood flow, cerebral blood volume, cerebral perfusion pressure, and intracranial pressure) and responds to changes in the pulmonary and cardiovascular condition of the patient simulator.


Chiral 1-phenylethylamine-derived phosphine-phosphoramidite ligands for highly enantioselective Rh-catalyzed hydrogenation of beta-(acylamino)acrylates: significant effect of substituents on 3,3'-positions of binaphthyl moiety.
A series of new chiral phosphine-phosphoramidite ligands with a 3,3'-substituted binaphthyl moiety were prepared from 1-phenylethylamine, and successfully applied in the Rh-catalyzed asymmetric hydrogenation of beta-(acylamino)-acrylates. The research disclosed that the substituents on the 3,3'-positions of binaphthyl moiety significantly influenced the enantioselectivity.


Oral hyposensitization to nickel induces clinical improvement and a decrease in TH1 and TH2 cytokines in patients with systemic nickel allergy syndrome.
Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed Systemic Ni Allergy Syndrome (SNAS). We aimed at evaluating whether oral administration of low nickel doses improved clinical conditions and modulated immunological aspects of SNAS, without significant side effects. Thirty-six SNAS patients were enrolled. Treatment started after 1-month of low-Ni diet and consisted in an incremental oral NiOH dose phase (0.3ng to 1.5 microg/week) followed by a 12-months maintenance phase (1.5 microg/week). Randomly, twenty-four patients added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients were allowed rescue medications (antihistamines and topical steroids). After 4 months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven IL13, IL5 and IFN-gamma release by peripheral blood mononuclear cells was evaluated before and after treatment. Twenty-three patients receiving NiOH and the 12 control patients completed the study. Evaluation of SNAS clinical severity (by VAS and drug consumption) showed a significant difference in favor of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH group and none in the control group tolerated Ni-rich food reintroduction. Release of all studied cytokines in culture supernatants was significantly lower after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and drug consumption in SNAS and is able to modulate inflammatory parameters.


Microarray-based copy number and expression profiling in dedifferentiated and pleomorphic liposarcoma.
Sixteen dedifferentiated and pleomorphic liposarcomas were analyzed by comparative genomic hybridization (CGH) to genomic microarrays (matrix-CGH), cDNA-derived microarrays for expression profiling, and by quantitative PCR. Matrix-CGH revealed copy number gains of numerous oncogenes, i.e., CCND1, MDM2, GLI, CDK4, MYB, ESR1, and AIB1, several of which correlate with a high level of transcripts from the respective gene. In addition, a number of genes were found differentially expressed in dedifferentiated and pleomorphic liposarcomas. Application of dedicated clustering algorithms revealed that both tumor subtypes are clearly separated by the genomic profiles but only with a lesser power by the expression profiles. Using a support vector machine, a subset of five clones was identified as "class discriminators." Thus, for the distinction of these types of liposarcomas, genomic profiling appears to be more advantageous than RNA expression analysis.


Prostate cancer: an evolving paradigm.
Since at least the early 1990s, stage and risk migration have been seen in patients with prostate cancer, likely corresponding to the institution of prostate specific antigen (PSA) screening in health systems. Preoperative risk factors, including PSA level and clinical stage, have decreased significantly. These improved prognostic variables have led to a larger portion of men being stratified with low-risk disease, as per the classification of D'Amico and associates. This, in turn, has corresponded with more favorable postoperative variables, including decreased extraprostatic tumor extension and prolonged biochemical-free recurrence rates. The advent of focal therapy is bolstered by findings of increased unilateral disease with decreased tumor volume. Increasingly, targeted or delayed therapies may be possible within the current era of lower risk disease.


The Use of Ultrasound Guidance for the Treatment of Raynaud Disease of the Hand With Botulinum Toxin.
This study sought to examine the feasibility and effectiveness of the use of ultrasound (US) as a clinical adjunct in the delivery of botulinum toxin for the treatment of Raynaud disease of the hand. One cadaver hand was injected with a colored simulation material using the current traditional surface anatomy approach, whereas an additional cadaver hand was injected using US guidance. The hands were dissected and areas of distribution of the simulation material were evaluated. Five patients diagnosed with Raynaud disease were treated with botulinum toxin using US guidance and data using the Patient-Reported Outcomes Measurement Information System Upper Extremity were collected. The cadaver hand injected with a colored simulation material using US guidance demonstrated significantly reduced surface area of muscle infiltrated compared with the cadaver hand injected using the traditional surface anatomy approach (16 cm vs 37 cm, P < 0.001).All 5 patients treated with botulinum toxin using US guidance reported significant improvement in symptoms and function after injection (P < 0.05), where zero patients reported intrinsic hand weakness. The use of US significantly improves the accuracy of delivery of a surrogate dye in a cadaver model of Raynaud disease, whereas its use clinically results in at least as effective a treatment as the landmark approach, but with less botulinum toxin required to achieve the clinical effect.


Cyclic nucleotides in cerebrospinal fluid of drug-free Parkinson patients.
Concentrations of cyclic nucleotides--adenosine-3',5'-monophosphate (c-AMP) and guanosine-3',5'-monophosphate (c-GMP)--were measured in cerebrospinal fluid (CSF) of 17 drug-free Parkinson patients and 12 controls. No significant difference between the cyclic nucleotide contents (p greater than 0.05) in CSF of patients and controls was detected, nor was there a correlation between the content and the degree of neurological disability. Besides, no changes in the cyclic nucleotide contents were detected in the subgroups of patients according to the prominence of tremor or rigidity/akinesia as the main symptoms of the disease.


"Multiligamentous" Injuries of the Skeletally Immature Knee: A Case Series and Literature Review.
Multiligamentous knee injuries occur rarely in the pediatric population. Few reports are available in the existing literature; furthermore, no longitudinal studies regarding the choice of treatment and long-term outcomes for this unique population have been published. To fill this knowledge gap, the literature on multiligamentous injuries of the knee in the adult population is commonly used as a guideline in clinical decision making for children and adolescents. However, the developing bone and physis are often weaker than the ligamentous structures of the knee-particularly during periods of rapid growth-and may be the first to fail in the event of injury or trauma. Bony avulsion fractures and peri-physeal fractures, rather than mid-substance ligamentous ruptures, may result. Patients with skeletal immaturity may therefore present with different patterns of multiligamentous injury after acute trauma to the knee. This article describes the clinical presentation, our treatment approach, and short-term outcomes for three pediatric patients with multiligamentous injuries of the knee and reviews the current literature relating to these uncommon injuries.


Acute Pancreatitis After the Use of Belimumab in a Patient With Systemic Lupus Erythematosus: Case Report and Review of Literature.
Belimumab is a B-cell depletion therapy that has emerged as an effective and safe treatment option for Systemic Lupus Erythematosus (SLE), but ongoing phase IV trials continue to report its common and rare adverse effects. Our case report seeks to add data to the existing literature on the safety profile of belimumab. We report an interesting and complicated case of a 30-year-old female with a 12-year history of SLE and multiple treatment failures who developed acute pancreatitis in the context of the initiation of belimumab. The temporal link between the two events made us undertake a review of literature on the efficacy and safety of belimumab. We used PubMed and Medline to shortlist eight studies that included phase III parent and extension clinical trials of belimumab that had been conducted in the past 10 years and illustrated the results in a tabulated form. The United States Food and Drug Administration has approved belimumab as a safe and effective treatment option for SLE. The BLISS-52, BLISS-76, and BLISS-SC trials along with their extension trials showed that SRI (SLE Responder Index) was higher in the patient cohorts that were treated with IV (intravenous) or SC (subcutaneous) belimumab. According to the website "eHealthMe.com", which tracks the incidence of adverse events from drugs by allowing people to report events, 14100 people reported side effects when taking belimumab and among them, 29 people (0.21%) reported acute pancreatitis. Time on belimumab when patients had acute pancreatitis was 1-2 years for 52% of the patients and 1-6 months for 40% of the patients; 96% of the patients were females. The age group at which it was most reported was 40-49 years. Additional data is needed to enable a better characterization of the pathophysiology and nature of acute pancreatitis as a possible side effect of belimumab.


Automated detection of anti-double-stranded DNA antibody in systemic lupus erythematosus serum by flow immunoassay.
We describe a novel automated flow immunoassay system for quantification of anti-double-stranded (ds) DNA autoimmune antibodies in the serum of patients suffering from systemic lupus erythematosus. dsDNA (360 bp) was covalently coupled with alkaline phosphatase (ALP) to form a novel analytical reagent (ALP-DNA). After immunoreaction, antibody-antigen complexes between ALP-DNA and anti-dsDNA monoclonal antibody were separated from unreacted ALP-DNA by an ion-exchange column on the basis of the difference in isoelectric point. Antibody-antigen complexes were subsequently quantified by luminescence following addition of 3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)phenyl- 1,2-dioxetane. The assay yielded a linear relationship between signal and concentration of anti-dsDNA monoclonal antibody in the range of 0-300 micrograms/mL. This simple technique permits the assay of anti-dsDNA autoimmune antibodies within 25 min. The ion-exchange column was simply regenerated by occasional elution with eluent (20 mM N-methylpiperazine, pH 5.5) supplemented with 0.5 M NaCl, to remove unreacted ALP-DNA.


Correlation between the levels of certain carcinogenic and anticarcinogenic trace elements and esophageal cancer in northern Iran.
Levels of four carcinogenic (Ni, Fe, Cu, Pb) and four anticarcinogenic (Zn, Se, Mn, Mg) trace elements were measured in hair samples from esophageal cancer patients, their unaffected family members, and members of families with no history of cancer. Measurements were also made in non-esophageal cancer patients, using atomic absorption spectroscopy, inductively coupled plasma-emission spectroscopy, and neutron activation analysis. The results showed that Ni and Cu concentrations were significantly higher and Mg and Mn concentrations were significantly lower in all cancer cases. Levels of Zn, Fe, Se, and Pb were not significantly different in the above-mentioned groups. In addition, the serum albumin fraction, which is reported to have antioxidant activity, was found to be significantly lower among esophageal cancer patients.


Internalization of D2 dopamine receptors is clathrin-dependent and select to dendro-axonic appositions in primate prefrontal cortex.
Much of our knowledge on trafficking of neurotransmitter receptors derives from heterologous expression systems and neurons in vitro. Understanding these dynamics in vivo for dopamine receptors, and D2 receptors (D2Rs) in particular, presents a foremost challenge as their pharmacological manipulation underlies antipsychotic medications and drug abuse, which may in turn alter response to endogenous dopamine. Here we present the first ultrastructural evidence of clathrin-mediated endocytosis of D2Rs or any other neurotransmitter receptor in the primate brain. We have captured in situ the insertion of D2Rs in clathrin-coated membrane pits, resulting in receptor sorting in primary endosomes. Endocytosis was specific to nonsynaptic membranes of distal dendrites, and virtually absent from larger shafts, spines, axons and perikarya expressing D2Rs. The selective association of D2Rs with the clathrin endocytotic pathway of high-order dendrites identifies a novel substrate for monitoring and adjusting dopaminoception, as well as a potent target for dysregulation, and manipulation, of D2R signalling in mental illness.


[Observation of neural electrophysiology and morphology in traumatic optic neuropathy in cat model].
To establish the animal model of traumatic optic neuropathy similar to clinical feature by injuring the optic nerve of the pipeline through the ethmoid and sphenoid sinus. The electrophysiology and morphology were observed. The optic nerve in 2 cats was anatomically observed. Thirty healthy adult cats were divided into 1 h, 1 d, 3 d, 1 w, 2 w, 4 w injury groups. The right eye was selected as the experiment eye, and the left as the control. The optic canals were damaged by the injury instrument. The changes of optic nerve were observed using light and electron microscope. The pattern reversal visual evoked potential (PR-VEP) was used to determine the succeed model and pupil was monitored. PR-VEP and neural tissue morphology were examined at intervals of 1 h, 1 d, 3 d, 1 w, 2 w, 4 w after trauma. Eight cats had Marcus-Gunn's pupil, and 22 cats did not have after injury. Neural tissue was physaliphorous degeneration in light microscope. The neural fibers swelled gradually and fibers physaliphorous degeneration in the first day after damage. At the seventh day, the bubble enlarged to be a big flat. After two weeks, the big flat bubble came out to be a bigger bubble. Under the electronic microscope, axons were physaliphorous degeneration, crack emerged between axon membrane and myelin sheath and myelin sheath were loose in the first day. At the third day, axon swelled, physaliphorous degeneration rose and myelin sheath were loose obviously. At the seventh day, axon and myelin sheath appeared loop in half cycle and bubble-like broke up. A lot of pieces came out and axon became physaliphorous and uniform. Microtubule and microfilament disappeared. After two weeks, myelin sheath became onion-like. On fourth week, myelin sheaths enlarged and squeezed to center. Axoplasm disappeared and neural tissues collapsed. This animal model was similar to clinical optic nerve decompression through ethmoid and sphenoid sinus. The change of PR-VEP and neuromorphology were distinct before and after trauma. The pathological changes of optic nerve catching vibrated injury are mainly degeneration, so earlier decompression of optic nerve may improve the visual function.


Prevention of bicycle-related injuries in childhood: role of the caregiver.
To assess perceptions of bicycle-related head injuries, helmet use, and safety practices, we had questionnaires distributed to caregivers of 2,500 children in the third through sixth grades; 1,006 (40.2%) completed surveys were returned. Eight hundred thirty-two caregivers (82.7%) indicated that they had a child cyclist in their household; approximately 65% responded that they believed head injury was likely if their child was involved in a bicycle mishap. A majority (approximately 70%) also said that a bicycle helmet may prevent head injury in between 25% and 75% of all occurrences. Yet 758 (91.1%) students did not own or have access to a bicycle helmet. Among the caregivers whose child did not have a bicycle helmet, 530 (69.9%) stated that they had never thought about purchasing one. Caregivers of both helmeted and nonhelmeted youngsters indicated concern for bicycle safety (100% versus 94%, respectively). Most caregivers (approximately 64%) stated that they would encourage their child to attend a bicycle safety camp. These findings suggest that caregivers perceive the dangers associated with bicycling but are not cognizant of available programs and methods that prevent the risk of serious injury to bicyclists.


Intra-articular fractures of the basilar joint of the thumb.
This article on intra-articular fractures of the basilar joint of the thumb discusses the biomechanical and treatment complexities of fractures involving the thumb carpometacarpal joint. This review focuses on the treatment of thumb carpometacarpal fractures and dislocations, consolidating current philosophy and rationale regarding operative and nonoperative treatment. Treatment recommendations are based upon principles established in previous clinical and biomechanical studies emphasizing fracture-specific modalities. Emphasis is placed on maintenance of articular congruity, fracture stability, early motion, and maximum return of function.


Bioconversion of Lignocellulosic Materials with the Contribution of a Multifunctional GH78 Glycoside Hydrolase from Xylaria polymorpha to Release Aromatic Fragments and Carbohydrates.
A bifunctional glycoside hydrolase GH78 from the ascomycete Xylaria polymorpha (XpoGH78) possesses catalytic versatility towards both glycosides and esters, which may be advantageous for the efficient degradation of the plant cell-wall complex that contains both diverse sugar residues and esterified structures. The contribution of XpoGH78 to the conversion of lignocellulosic materials without any chemical pretreatment to release the water-soluble aromatic fragments, carbohydrates, and methanol was studied. The disintegrating effect of enzymatic lignocellulose treatment can be significantly improved by using different kinds of hydrolases and phenoloxidases. The considerable changes in low (3 kDa), medium (30 kDa), and high (> 200 kDa) aromatic fragments were observed after the treatment with XpoGH78 alone or with this potent cocktail. Synergistic conversion of rape straw also resulted in a release of 17.3 mg of total carbohydrates (e.g., arabinose, galactose, glucose, mannose, xylose) per gram of substrate after incubating for 72 h. Moreover, the treatment of rape straw with XpoGH78 led to a marginal methanol release of approximately 17 μg/g and improved to 270 μg/g by cooperation with the above accessory enzymes. In the case of beech wood conversion, the combined catalysis by XpoGH78 and laccase caused an effect comparable with that of fungal strain X. polymorpha in woody cultures concerning the liberation of aromatic lignocellulose fragments.


Effect of bromazepam on growth hormone and prolactin secretion in normal subjects.
The growth hormone and prolactin response to oral bromazepam (3 mg) was assessed in 5 normal men and 5 normal women. A peak growth hormone response of 11.9 +/- 3.7 ng/ml (mean +/- SD), significantly above the baseline (p less than 0.01), was achieved in the men. On the other hand, there was no statistically significant response of growth hormone secretion in the women. No change in prolactin secretion was observed in either sex.


Influence of Periodontal Status and Prosthetic Treatment on Survival and Success Rates in Implant Therapy: A 5-Year Retrospective Follow-Up Study.
The objective of the present study was to evaluate the 5-year outcome of dental implant therapy and assess the survival, success, and biological and technical complications. A periodontal and prosthetic-oriented evaluation was conducted on the variables that can influence the long-term predictability of implant therapy. A total of 615 patients and 1427 dental implants from a private clinic (MedArtis Dent, Cluj-Napoca, Romania) were enrolled in the study. The study was a longitudinal cohort with data collected retrospectively from physical/digital dental records in combination with a cross-sectional clinical/radiological examination. Results showed that periodontal diagnosis at baseline had a significant impact on the marginal bone loss prediction. Data showed that the cylindrical implant with an internal 45° medium taper connection experienced a higher rate of bone resorption compared to the tapered implant with the 5° internal connection. Screw-retained restorations and overdentures showed a statistical decrease in the marginal bone level height when compared to the cemented restorations. Data from our study suggest that not only is there a powerful association between recall visits and the rate of complications in dental implant treatment, but a lack of professional maintenance predicts a higher bone level loss during the 5-year interval.


Next-generation immunotherapies for lymphoma: one foot in the future.
Improved understanding of the interactions between cancer cells and the immune system combined with technological advances has led to the development of novel types of immunotherapies. These include checkpoint inhibitors, T-cell engager antibodies and chimeric antigen receptor T cells which have demonstrated remarkable efficacy in B-cell malignancies, including anti-PD1 antibodies in Hodgkin lymphoma, and T-cell engager antibodies and chimeric antigen receptor T cells in B-cell acute lymphoblastic leukemia, leading to their approval in these indications. Recent clinical data suggest that these immunotherapies may also benefit patients with other types of hematologic malignancies, particularly patients with Hodgkin and non-Hodgkin lymphomas. Here, we review the most recent clinical data regarding these different immunotherapies in patients with lymphoma. Ongoing and future studies should further define which immunotherapy may best apply to a given patient in order to provide a 'personalized immunotherapy'.


Facile synthesis of graphene/metal nanoparticle composites via self-catalysis reduction at room temperature.
Graphene/metal nanoparticle (NP) composites have attracted great interest for various applications as catalysts, electrodes, sensors, etc., due to their unique structures and extraordinary properties. A facile synthesis of graphene/metal NP composites with good control of size and morphology of metal NPs is critical to the practical applications. A simple method to synthesize graphene/metal NPs under a controllable manner via a self-catalysis reduction at room temperature has been developed in this paper. At first, metal NPs with desirable size and morphology were decorated on GO and then used as catalyst to accelerate the hydrolysis reaction of NaBH4 to reduce the graphene oxide. Compared to the existing methods, the method reported here features several advantages in which graphene/metal NPs are prepared without using toxic and explosive reductant, such as hydrazine or its derivatives, making it environmentally benign, and the reaction can be processed at room temperature with high efficiency and in a large range of pH values. The approach has been demonstrated to successfully synthesize graphene composites with various metal NPs in large quantity, which opens up a novel and simple way to prepare large-scale graphene/metal or graphene/metal oxide composites under mild conditions for practical applications. For example, graphene/AuNP composites synthesized by the method show excellent catalytic capability.


On the successful use of a simplified model to simulate the succession of toxic cyanobacteria in a hypereutrophic reservoir with a highly fluctuating water level.
Many freshwater bodies worldwide that suffer from harmful algal blooms would benefit for their management from a simple ecological model that requires few field data, e.g. for early warning systems. Beyond a certain degree, adding processes to ecological models can reduce model predictive capabilities. In this work, we assess whether a simple ecological model without nutrients is able to describe the succession of cyanobacterial blooms of different species in a hypereutrophic reservoir and help understand the factors that determine these blooms. In our study site, Karaoun Reservoir, Lebanon, cyanobacteria Aphanizomenon ovalisporum and Microcystis aeruginosa alternatively bloom. A simple configuration of the model DYRESM-CAEDYM was used; both cyanobacteria were simulated, with constant vertical migration velocity for A. ovalisporum, with vertical migration velocity dependent on light for M. aeruginosa and with growth limited by light and temperature and not by nutrients for both species. The model was calibrated on two successive years with contrasted bloom patterns and high variations in water level. It was able to reproduce the measurements; it showed a good performance for the water level (root-mean-square error (RMSE) lower than 1 m, annual variation of 25 m), water temperature profiles (RMSE of 0.22-1.41 °C, range 13-28 °C) and cyanobacteria biomass (RMSE of 1-57 μg Chl a L-1, range 0-206 μg Chl a L-1). The model also helped understand the succession of blooms in both years. The model results suggest that the higher growth rate of M. aeruginosa during favourable temperature and light conditions allowed it to outgrow A. ovalisporum. Our results show that simple model configurations can be sufficient not only for theoretical works when few major processes can be identified but also for operational applications. This approach could be transposed on other hypereutrophic lakes and reservoirs to describe the competition between dominant phytoplankton species, contribute to early warning systems or be used for management scenarios.


Factors that contribute to underrecognition of delirium by registered nurses in acute care settings: a scoping review of the literature to explain this phenomenon.
In order to obtain more information regarding this phenomenon, a scoping review of the literature was undertaken to analyse current research on the recognition of delirium by registered nurses in acute care settings. Delirium is often manifested as a sign of an underlying undiagnosed condition that requires immediate intervention and is frequently manifested in acute care settings. Unfortunately, registered nurses often do not recognise delirium and its occurrence goes under-reported. Based on six inclusion criteria, a search in numerous databases using terms such as delirium detection, recognition and diagnosis by registered nurses was undertaken. Eight quantitative studies were deemed relevant and analysed for this scoping review. Seven major categories emerged: the fluctuating nature of delirium, the impact of delirium education on its recognition, communication barriers, inadequate use of delirium assessment tools, lack of conceptual understanding of delirium, delirium as a burden and the likeness of delirium and dementia. A brief summary of the findings in each category is reported here. The scoping review revealed that delirium remains underrecognised by registered nurses, which potentially contributes to reduced quality of nursing care for clients experiencing this condition. Further research on delirium and the processes that registered nurses use to recognise it is timely and will facilitate the development of evidence-based interventions to manage it. While acute care registered nurses have historically reported dramatic changes in cognitive and neuro-biological functions in ill older adults, the literature highlighted in this scoping review revealed the following: (1) the need for further research to validate delirium assessment tools and, (2) the need for education and training for registered nurses on the use of these assessment tools to promote early recognition and thereby decrease the incidence of delirium in older adults.


Muscarinic-dependent phosphorylation of the cardiac ryanodine receptor by protein kinase G is mediated by PI3K-AKT-nNOS signaling.
Post-translational modifications of proteins involved in calcium handling in myocytes, such as the cardiac ryanodine receptor (RyR2), critically regulate cardiac contractility. Recent studies have suggested that phosphorylation of RyR2 by protein kinase G (PKG) might contribute to the cardioprotective effects of cholinergic stimulation. However, the specific mechanisms underlying these effects remain unclear. Here, using murine ventricular myocytes, immunoblotting, proximity ligation as-says, and nitric oxide imaging, we report that phosphorylation of Ser-2808 in RyR2 induced by the muscarinic receptor agonist carbachol is mediated by a signaling axis comprising phosphoinositide 3-phosphate kinase, Akt Ser/Thr kinase, nitric oxide synthase 1, nitric oxide, soluble guanylate cyclase, cyclic GMP (cGMP), and PKG. We found that this signaling pathway is compartmentalized in myocytes, as it was distinct from atrial natriuretic peptide receptor-cGMP-PKG-RyR2 Ser-2808 signaling and independent of muscarinic-induced phosphorylation of Ser-239 in vasodilator-stimulated phosphoprotein. These results provide detailed insights into muscarinic-induced PKG signaling and the mediators that regulate cardiac RyR2 phosphorylation critical for cardiovascular function.


Use of Natural Family Planning (NFP) and Its Effect on Couple Relationships and Sexual Satisfaction: A Multi-Country Survey of NFP Users from US and Europe.
Birth control is a persistent global health concern. Natural family planning (NFP) comprises methods to achieve or avoid pregnancy independent of mechanical or pharmacological intervention. The sympto-thermal method (STM) of NFP employs daily observation of cervical fluids and measurement of basal body temperature. This multi-country study was undertaken to describe the characteristics of STM users, understand their perceptions of NFP, and its perceived impact on relationships. Questionnaires for women and men were developed in German and translated to English, Polish, Italian, Czech, and Slovak by native speakers. A total of 2,560 respondents completed the online questionnaire (37.4% response). Participants were married (89%) and well educated, and their self-perceived financial status was described as "good" or "very good" by 65% of the respondents. Forty-seven percent had previously used contraceptives. Ninety-five percent of women and 55% of men said using NFP has helped them to know their body better. Large majorities of men (74%) and women (64%) felt NFP helped to improve their relationship while <10% felt use of NFP had harmed their relationship. Most women (53%) and men (63%) felt using NFP improved their sex life while 32% of women and 24% of men felt it was unchanged from before they used NFP. Seventy-five percent of women and 73% of men said they are either "satisfied" or "very satisfied" with their frequency of sexual intercourse. This survey demonstrates STM of NFP is a well-accepted approach to family planning across several Western cultures. It is consistently viewed as being beneficial to couples' self-knowledge, their relationship, and satisfaction with frequency of sexual intercourse.


An efficient chromatin immunoprecipitation (ChIP) protocol for studying histone modifications in peach reproductive tissues.
Perennial fruit trees display a growth behaviour characterized by annual cycling between growth and dormancy, with complex physiological features. Rosaceae fruit trees represent excellent models for studying not only the fruit growth/patterning but also the progression of the reproductive cycle depending upon the impact of climate conditions. Additionally, current developments in high-throughput technologies have impacted Rosaceae tree research while investigating genome structure and function as well as (epi)genetic mechanisms involved in important developmental and environmental response processes during fruit tree growth. Among epigenetic mechanisms, chromatin remodelling mediated by histone modifications and other chromatin-related processes play a crucial role in gene modulation, controlling gene expression. Chromatin immunoprecipitation is an effective technique to investigate chromatin dynamics in plants. This technique is generally applied for studies on chromatin states and enrichment of post-transcriptional modifications (PTMs) in histone proteins. Peach is considered a model organism among climacteric fruits in the Rosaceae family for studies on bud formation, dormancy, and organ differentiation. In our work, we have primarily established specific protocols for chromatin extraction and immunoprecipitation in reproductive tissues of peach (Prunus persica). Subsequently, we focused our investigations on the role of two chromatin marks, namely the trimethylation of histone H3 at lysine in position 4 (H3K4me3) and trimethylation of histone H3 at lysine 27 (H3K27me3) in modulating specific gene expression. Bud dormancy and fruit growth were investigated in a nectarine genotype called Fantasia as our model system. We present general strategies to optimize ChIP protocols for buds and mesocarp tissues of peach and analyze the correlation between gene expression and chromatin mark enrichment/depletion. The procedures proposed may be useful to evaluate any involvement of histone modifications in the regulation of gene expression during bud dormancy progression and core ripening in fruits.


Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.
To explore the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNAs in oesophageal squamous cell carcinoma (ESCC) in order to construct an oesophageal cancer-specific competing endogenous RNA (ceRNA) network. In this work, the expression data of miRNAs, lncRNAs, and mRNAs in ESCC were obtained. An oesophageal cancer-specific ceRNA network was then constructed and investigated. CeRNAs have the ability to reduce the targeting activity of miRNAs, leading to the de-repression of specific mRNAs with common miRNA response elements. CeRNA interactions have a critical effect in gene regulation and cancer development. This study suggests a novel perspective on potential oesophageal cancer mechanisms as well as novel pathways for modulating ceRNA networks for treating cancers.


[Preparation and pharmacologic activity of N-oxides of 4'-(benzotriazol-2-yl-phenylalkanoic and -phenoxyalkanoic acids].
A number of N-oxides of 4'-(benzotriazol-2-yl)-phenylalkanoic and -phenoxyalkanoic acids bearing various substituents on position 6 of benzotriazole together with 4'-(benzotriazol-2-yl) phenylacetic acid were prepared and subjected to a wide pharmacological screening. Several compounds exhibited significant antiinflammatory and diuretic activities, while one was endowed with antihypertensive activity.


[Antioxidant properties of estrogens].
The author expounded present state of knowledge concerning antioxidant properties of estrogens. Estradiol, apart from its main hormonal effect, probably displays two mechanisms of antioxidant action. One of them results from hydroxyphenolic structure of their molecule. Estradiol may donate hydrogen atoms from its phenolic hydroxyl group to lipid peroxyradicals what results in the termination of the chain reactions of cell membrane phospholipides, which are the key reactions in cell damage. Estradiol also inhibits oxidative modification of LDL lipoprotein which plays the main role in atherogenesis. The other mechanism of antioxidative action of estradiol is probably associated with its stimulatory effect on natural cellular antioxidant enzymes. Data on this subject are scarce and controversial. The mechanisms of antioxidant action of estrogens require further investigation.


Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36.
Paeonol, a potent antioxidant isolated from cortex moutan, possesses athero‑protective activity, yet the detailed mechanisms are not fully investigated. This study was conducted to explore the role of paeonol and its underlying mechanisms in RAW264.7 macrophages and apolipoprotein E‑deficient (ApoE(‑/‑)) mice. Paeonol treatment significantly attenuated intracellular lipid accumulation in macrophages, which may be the result of decreased oxidized low‑density lipoprotein (ox‑LDL) uptake and increased cholesterol efflux. Additionally, paeonol markedly inhibited the mRNA and protein expression of the cluster of differentiation 36 (CD36) by decreasing nuclear translocation of c‑Jun [a subunit of activator protein‑1 (AP‑1)]. Moreover, paeonol upregulated the protein stability of ATP‑binding cassette transporter A1 (ABCA1) by inhibiting calpain activity, while ABCA1 mRNA expression was not altered. Furthermore, small hairpin RNA (shRNA) targeting haem oxygenase‑1 (HO‑1) inhibited the paeonol‑mediated beneficial effects on the expression of c‑Jun, CD36, ABCA1, calpain activity and lipid accumulation in macrophages. Accordingly, paeonol retarded the progress of atherosclerosis in ApoE(‑/‑) mice and modulated the expression of CD36 and ABCA1 in aortas similarly to that observed in macrophages. These results indicate that paeonol provides protective effects on foam cell formation by a novel HO‑1‑dependent mediation of cholesterol efflux and lipid accumulation in macrophages.


Detection and quantitation of human enteric viruses in waste waters: increased sensitivity using a human immune serum globulin--immunoperoxidase assay on MA-104 cells.
This study demonstrates that the most sensitive method for the detection and quantitation of cultivable human enteric viruses in water samples after repassage in the MA-104 cell line is the detection of infected cells by the human immune serum globulin--immunoperoxidase (HISG-IP) method recently described by the authors. This immunoperoxidase method is up to 50 times more sensitive than a liquid overlay assay by cytopathic effect in BGM cells. The viral content of waste waters was evaluated with this new methodology. By this method the average viral content of raw sewage (RS) was 900 mpniu/L (most probable number of infectious units per litre), 1056 mpniu/L in primary effluent (PE), and 106 mpniu/L in secondary effluent (SE). With a cytopathic effect assay on BGM cells, values of 85 (RS), 56 (PE), and 2 (SE) mpniu/L were observed, a striking underestimation of the viral content of secondary effluents.


Dentists' Prescribing of Analgesics for Children in British Columbia, Canada
Recently, there has been great interest in the use, abuse and over-prescribing of opioid analgesics for children. However, there is a paucity of evidence on patterns of prescribing of both narcotic and non-narcotic analgesics for children by dentists. We used a population-wide prescription drug database (PharmaNet) in British Columbia, Canada, to examine prescribing and dispensing of analgesics surrounding dental procedures. We examined all drugs prescribed for children by dentists between 1997 and 2013, as we had access to data on drug doses and days of medication supply. We also examined trends in the use of various narcotic and non-narcotic analgesics and benzodiazepines. In total, 268 691 children were prescribed at least 1 study drug by a dentist. Codeine was the most frequently prescribed: 50% of children received codeine for more than 3 days. Duration of use of codeine was greatest among children ≥12 years, the longest duration of use being 5 days. Our study reveals that codeine prescription by dentists increased over the 16-year study period. Codeine is prescribed by dentists for 50% of children; prescriptions are for too long a duration to avoid potential morphine accumulation and are not in line with current treatment guidelines.


Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital.
To determine whether the tumour necrosis factor-alpha (TNF-alpha) antagonist adalimumab (Humira) can be efficacious after secondary loss of efficacy (i.e. loss of clinical response in patients who had initially demonstrated clinical response) to infliximab (Remicade) or etanercept (Enbrel). We studied 36 patients from the Stockholm TNF-alpha follow-up registry (STURE) who received adalimumab after secondary loss of efficacy to infliximab (group A, n = 27) or etanercept (group B, n = 9), and 26 patients who were started on adalimumab as the first TNF-alpha antagonist (group C). In group A, the baseline disease activity score 28 (DAS28) at infliximab institution was 5.5+/-0.2. During infliximab treatment, the mean best DAS28 was 3.7+/-0.2 (p<0.001), but increased to 5.2+/-0.3 when infliximab was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.5+/-0.3 (p<0.003), and then to 4.2+/-0.2 at 6 months (p<0.001). In group B, the baseline DAS28 at etanercept institution was 6.6+/-0.5. During etanercept treatment, the mean best DAS28 was 4.6+/-0.5 (p<0.01), but increased to 5.7+/-0.4 by the time etanercept was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.8+/-0.3 (p<0.005), and to 4.1+/-0.2 at 6 months (p<0.001). In group C, the mean baseline DAS28 was 5.6+/-0.3. After 6 months of adalimumab therapy, the DAS28 decreased to 3.5+/-0.4 (p<0.001). ACR20 responses with adalimumab in groups A, B, and C were similar (70-78%). For patients with secondary loss of efficacy from infliximab or etanercept, switching to adalimumab can restore a good clinical response.


Temporal regulation of peripheral BDNF levels during cocaine and morphine withdrawal: comparison with a natural reward.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has long been studied in the field of addiction and its importance in regulating drug addiction-related behavior has been widely demonstrated. The aim of our study was to analyze the consequences of a repeated exposure to drugs of abuse or natural reward on plasma BDNF levels during withdrawal. Rats were chronically injected with morphine (subcutaneously, 5mg/kg) or cocaine (intraperitoneally, 20mg/kg) or fed with a butter biscuit (per os, 4g) once per day for 14 days. Blood collection was performed on the 1st (withdrawal day 1 or WD1) or on (WD14), either at the same time point rats had been exposed to drugs or natural reward or at a different time point (used to quantify basal brain-derived neurotrophic factor levels). Cocaine treatment led to a rapid (WD1) and persistent (WD14) decrease of basal BDNF levels compared with saline-treated animals, whereas morphine induced an increase on WD14 without any alteration on WD1. On the contrary, the natural reward induced a significant increase of basal brain-derived neurotrophic factor levels only on WD1. The analysis of BDNF levels at the usual time point at which animals had been exposed showed that both drugs, but not the natural reward, increased BDNF levels compared with basal levels. Our data highlight that only drugs of abuse are able to persistently alter BDNF levels and to induce specific variations of this neurotrophic factor at the usual hour of injection.


Ureteral obstruction as a complication of renal transplantation: a review.
Ureteral obstruction in a renal allograft, due to a variety of etiologies, is both a challenging diagnostic and therapeutic disorder. Since ureteral obstruction in a renal transplant recipient usually presents as azotemia, it must also be distinguished from acute rejection. Although ultrasound is non-invasive and readily available, the most definitive diagnostic tool is percutaneous nephrostomy tube placement with antegrade nephrostogram. A variety of therapeutic approaches are available to treat ureteral obstruction in a renal allograft. These procedures can be open (e.g., repeat ureteroneocystotomy) or utilize an endourological approach (e.g., transluminal ureteral dilatation). From an experimental standpoint, recent data in rodent models of experimental hydronephrosis demonstrate similar pathobiologic events in both the obstructed kidney and an allograft undergoing the chronic rejection process. To this end, investigation needs to be conducted to assess whether partial, unrecognized ureteral obstruction in an allograft hastens the development of chronic rejection. This would further underscore the importance of ureteral obstruction as a cause for not only acute azotemia in an allograft, but also chronic deterioration in renal transplant function.


Analysis of fecal microbial flora for antibiotic resistance in ceftiofur-treated calves.
To evaluate the impact of ceftiofur treatment in calves on fecal shedding of ceftriaxone-resistant bacteria, 3 female Holstein dairy calves were treated by intramuscular injection with EXCENEL RTU (ceftiofur hydrochloride, Pharmacia and Upjohn) at a therapeutic dosage of 2.2 mg/kg/day for 5 consecutive days following label directions. Three untreated calves were housed separately and served as controls. One to 3 days following the initial administration of ceftiofur, there was a 14% and 2% increase of fecal bacteria resistant to 16 and 64 microg ceftriaxone/mL, respectively. This response remained unchanged from days 6 to 13, and increased resistance was seen at day 17. Randomly selected isolates of gram-positive and gram-negative bacteria with elevated resistance to ceftriaxone (minimal inhibitory concentration (MIC) >or=64 microg ceftriaxone/mL) were isolated from calf feces and identified. In vitro conjugation experiments revealed that both the ceftriaxone-resistance gene bla (CMY-2) and class 1 integron were transferred from two bacterial species to Salmonella spp. at a frequency of 10(7) to 10(5). MIC data revealed that Salmonella transconjugants acquired either reduced susceptibility or resistance to ceftriaxone as well as to multiple antibiotics. This genetic transfer occurred both within and between genera. Treatment of calves with therapeutic dosages of ceftiofur can significantly increase for at least 17 days following the initial treatment the fecal excretion of ceftriaxone-resistant bacteria, including Salmonella species.


Arthroscopic treatment of glenoid labral tears.
We reviewed 52 consecutive patients who had undergone arthroscopic labral debridement. The average age was 29 and there were 35 men and 17 women. At operation, 27 patients had superior labrum anterior and posterior (SLAP) lesions, 20 patients had anteroinferior labral lesions, and 5 patients had posterior labral lesions. Despite the fact that, preoperatively, none of these patients had a history of dislocations or clinically evident instability, 70% of the patients with superior labral lesions, and all of those with anteroinferior and posterior lesions had instability on examination under anesthesia. The average followup was 36 months. At 1 year after arthroscopy, 78% of the patients with superior lesions had excellent relief compared with 30% of the patients in the anteroinferior group. At 2 years followup, these results decreased to 63% and 25%, respectively, and only 45% of the patients with superior labral lesions and 25% of those with anteroinferior lesions had returned to their previous athletic performance level. Four patients required a reoperation: 2 for instability and 2 for impingement. We conclude that occult instability is frequently present in patients with glenoid labral tears. The overall results are not encouraging, but this procedure may have an indication for short-term goals in competitive athletes or those who are willing to accept some compromise in function.


Organ Preservation Strategies in Laryngeal Chondrosarcoma.
Laryngeal chondrosarcoma (LC) is a rare, slowly growing malignancy. The preferred treatment is laryngeal preservation surgery (LPS). Some patients may require multiple interventions or total laryngectomy (TL). We investigated risk factors for retreatment and TL, and assessed the impact of LPS on oncological and functional outcomes. Case series METHODS: We searched our institution database for LC. Tumor grading, localization, and margin status were tested as predictors of recurrence and organ preservation. We included 21 patients (seven females, mean age 58 ± 12 years). LPS was applied in 20 (95.2%) of them as a primary procedure. Six patients were treated by transoral approach and 14 received "open-neck" LPS. Fifteen (71.4%) were operated only once, while six patients underwent a total of 15 adjunctive procedures. Additional operations were always performed for recurrence of tumors localized within the cricoid plate. The histological grading was G1 in 81% and G2 in 19%. However, two patients with a primary G1 LC showed a G2 recurrence. Reoperations for recurrence were more frequent among patients with G2 in respect to G1 histology (83% vs. 7%, P < .001). Fifty percent of G2 LC and 8% of G1 underwent TL (P < .05). Margin status had no influence on recurrence rate. Patients with G2 LC have more recurrences requiring surgery and a higher incidence of TL. Cricoid plate localization is relevant for organ preservation. Margin status signals possible disease persistence, without influencing the need for future surgeries. Need for reoperation entails a risk of not being able to maintain organ functionality. 4 Laryngoscope, 132:838-843, 2022.


Identification and validation of sRNAs in Edwardsiella tarda S08.
Bacterial small non-coding RNAs (sRNAs) are known as novel regulators involved in virulence, stress responsibility, and so on. Recently, a lot of new researches have highlighted the critical roles of sRNAs in fine-tune gene regulation in both prokaryotes and eukaryotes. Edwardsiella tarda (E. tarda) is a gram-negative, intracellular pathogen that causes edwardsiellosis in fish. Thus far, no sRNA has been reported in E. tarda. The present study represents the first attempt to identify sRNAs in E. tarda S08. Ten sRNAs were validated by RNA sequencing and quantitative PCR (qPCR). ET_sRNA_1 and ET_sRNA_2 were homolous to tmRNA and GcvB, respectively. However, the other candidate sRNAs have not been reported till now. The cellular abundance of 10 validated sRNA was detected by qPCR at different growth phases to monitor their biosynthesis. Nine candidate sRNAs were expressed in the late-stage of exponential growth and stationary stages of growth (36~60 h). And the expression of the nine sRNAs was growth phase-dependent. But ET_sRNA_10 was almost expressed all the time and reached the highest peak at 48 h. Their targets were predicted by TargetRNA2 and each sRNA target contains some genes that directly or indirectly relate to virulence. These results preliminary showed that sRNAs probably play a regulatory role of virulence in E. tarda.


Evaluation of Retinal Nerve Fiber Layer, Ganglion Cell-Inner Plexiform Layer, and Optic Nerve Head in Glaucoma Suspects With Varying Myopia.
Myopic glaucoma suspects, particularly with high myopia, experience thinning of nontemporal parameters of retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL), without change in optic nerve head (ONH) parameters. The aim was to assess the effect of myopia on RNFL, GCIPL, and ONH parameters in glaucoma suspects. Seventy-six eyes of glaucoma suspects studied with Cirrus high definition optical coherence tomography were divided into low (n=27), moderate (n=25), and high myopia (n=24) groups. Optical coherence tomography parameters were correlated with spherical equivalent (SE) and evaluated with areas under the receiver operating characteristic curve for quantifying diagnostic ability to differentiate high myopia from nonhigh myopia. In high myopia, SE was positively correlated with thinning of average, minimum, and nontemporal GCIPL and thinning of average and nontemporal RNFL (P<0.05 for all), but not for inferior RNFL (P=0.28). In moderate myopia, SE was correlated with thinning of inferonasal and minimum GCIPL as well as superior and inferior RNFL (P<0.05 for all). SE was not correlated with ONH parameters in moderate or high myopia (P>0.05). The largest areas under the receiver operating characteristic curve for RNFL and GCIPL parameters were for superior (0.82) and superonasal (0.80) regions, respectively, with comparable diagnostic ability (P=0.74). High myopia, in particular, is associated with thinning of average RNFL, average and minimum GCIPL, and nontemporal parameters of both RNFL and GCIPL, warranting consideration of refractive status in glaucoma suspects.


Associations between Bone Material Strength Index, Calcaneal Quantitative Ultrasound, and Bone Mineral Density in Men.
Impact micro-indentation (IMI) measures bone material strength index (BMSi) in vivo. This study investigated how IMI is associated with calcaneal quantitative ultrasound and bone densitometry parameters in men. BMSi was measured on the tibial plateau using the OsteoProbe in 377 men (age 33-96 years) from the Geelong Osteoporosis Study. Broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) were assessed at the calcaneus using an ultrasonometer. Areal BMD was measured at several skeletal sites using dual-energy x-ray absorptiometry. Linear associations between parameters were tested using Pearson's correlation. Multivariable regression techniques were used to determine associations between BMSi and other measures of bone, independent of confounders. BMSi was negatively correlated with age (r = -0.171, P = .001), weight (r = -0.100, P = .052), and body mass index (r = -0.187, P = .001), and positively with height (r = +0.109, P = .034). There was some evidence to support a positive association between BMSi and BUA (β = 0.052, P = .037), SOS (β = 0.013, P = .144), and SI (β = 0.036, P = .051). After age adjustment, this association was attenuated. No correlations were observed between BMSi and BMD at any skeletal site (r values ranged from -0.006 to +0.079, all P ≥ .13). There was a small positive association between BMSi and quantitative ultrasound (QUS) parameters, which were not independent of age. No associations were detected between BMSi and BMD. This suggests that BMSi and QUS are capturing common age-dependent properties of bone. Further research on the utility of IMI alone and complementary to conventional bone testing methods for predicting fracture risk is warranted.


Two-Dimensional Boron-Rich Monolayer BxN as High Capacity for Lithium-Ion Batteries: A First-Principles Study.
Owing to lightweight, abundant reserves, low cost, and nontoxicity, B-based two-dimensional (2D) materials, e.g., borophene, exhibit great potential as new anode materials with higher energy density for Li-ion batteries (LIBs). However, exfoliation of borophene from the Ag substrate remains the most daunting challenge due to their strong interfacial interactions, significantly restricting its practical applications. In this study, through first-principles swarm-intelligence structure calculations, we have found several Boron-rich boron nitride BxN materials (x = 2, 3, 4, and 5) with increased stability and weakened interactions with the Ag(111) substrate compared with δ6-borophene. A high cohesive energy and superior dynamical, thermodynamic, and mechanical stability provide strong feasibility for their experimental synthesis. The obtained BxN materials exhibit a high mechanical strength (94-226 N/m) and low interfacial bonding with the Ag substrate, from -0.043 to -0.054 eV Å-2, significantly smaller than that of δ6-borophene. Among them, B3N and B5N exhibit not only a remarkably high storage capacity of 1805-3153 mAh/g but also a low barrier energy and open-circuit voltage. Moreover, B2N showed a cross-sheet motion with a low barrier of 0.24 eV, which is unique compared with the in-plane diffusion in most other 2D electrode materials restricted by their quasi-flat geometry. BxN also exhibits excellent cyclability with improved metallic conductivity upon Li-ion intercalation, showing great potential in LIB applications. This study opens up a new avenue to explore B-rich 2D electrode materials in energy applications and provide instructive insights into borophene functionalization and exfoliation.


A cross-linked complex between ferredoxin and ferredoxin-NADP+ reductase.
The water-soluble carbodiimide, N-ethyl-3-(3-dimethylaminopropyl)carbodiimide was found to effectively cross-link ferredoxin to ferredoxin-NADP+ reductase. The covalent complex has a stoichiometry of 1 mol of ferredoxin per mol of the reductase. The flavoprotein moiety of the cross-linked complex maintains most of its diaphorase activity and more interestingly has gained the capacity to catalyze the NADPH-cytochrome c reaction without addition of free ferredoxin in the assay mixture. Furthermore, the cross-linked complex binds NADP+ with a Kd = 88 microM at an ionic strength of 0.02 M. These results show that a ternary complex among the reductase and its substrates can be formed, suggesting that the binding sites for ferredoxin and the pyridine nucleotides are distinct. The bound ferredoxin can interact with cytochrome c; the iron-sulfur cluster of the cross-linked complex is shown to be reduced under anaerobic conditions by NADPH and to be required for the catalysis of the NADPH-cytochrome c reductase reaction. The cross-linked complex, added to thylakoids inhibited by the antibody against the reductase, catalyzes the H2O-cytochrome c photoreduction, which suggests that the ferredoxin moiety of the complex can interact with its electron donor in the photosynthetic chain. Restoration of NADP+ photoreduction requires the addition of free ferredoxin.


Phonon line emission revealed by self-assembly of colloidal nanoplatelets.
We show that colloidal nanoplatelets can self-assemble to form a 1D superlattice. When self-assembled, an additional emission line appears in the photoluminescence spectrum at low temperatures. This emission line is a collective effect, greatly enhanced when the NPLs are self-assembled. It is attributed to the longitudinal optical (LO) phonon replica of the band-edge exciton, and its presence in self-assembled nanoplatelets is explained using a model based on an efficient photons reabsorption between neighboring nanoplatelets. The presence of phonon replica at low temperatures in ensemble measurements suggests the possibility to design a laser, based on self-assembled nanoplatelets.


The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients.
The pharmacokinetics of fluconazole after a single 100 mg i.v. dose were studied in 10 healthy subjects (5 M; 5 F) and 10 HIV-positive patients (8 M; 2 F). The mean value of plasma clearance was 25% lower in the patient groups (17 +/- 6 (s.d.) vs 23 +/- 4 ml min-1; 95% CI of difference -11 to -0.7; P < 0.05). This difference may have been related to slightly reduced kidney function in the patient group (mean creatinine clearance -18%) but is unlikely to be clinically significant. Therefore, no adjustment of the dose of intravenously administered fluconazole appears to be necessary in AIDS patients without clinical signs of enteropathy.